Organ donation by minors has long been a highly controversial topic in both legal and ethical discussions worldwide. In the United States, case law has established a case-by-case review mechanism, allowing limited room for the practice of living organ donation by minors under specific conditions. Germany, with a strong emphasis on the protection of personal dignity, adopts a more cautious stance. In China, the law clearly stipulates that living organ donors must possess full civil capacity. However, some scholars argue that under strict conditions and with adequate safeguards, minors should be allowed to donate organs in emergency medical situations. Given the limited domestic experience in this area, China should develop a protective pathway that balances scientific validity, legal compliance, and humanistic concern, in line with its national conditions, legal traditions and cultural background, all under the guidance of the principle of caution. Based on a review of China’s current organ donation system, this article examines legislative philosophies, procedural designs and ethical review mechanisms in the U.S. and Germany. From a comparative law perspective, it extracts institutional elements that could serve as references, with the aim of improving China’s legal framework for organ donation by minors.

OBJECTIVE: To investigate the genetic mechanism for adverse pregnancies due to submicroscopic chromosomal structural variants in two cases, and to provide a precise guidance for preimplantation genetic testing. METHODS: Two families who had visited Chengdu Women's and Children's Central Hospital for reproduction guidance due to recurrent miscarriages, adverse pregnancy history and abnormal genetic testing of the offspring in June and December 2023 were selected as the study subjects. Chromosomal karyotyping and optical genome mapping (OGM) were carried out on peripheral blood samples from the two couples, and preimplantation genetic testing for structural rearrangement (PGT-SR) were performed on the blastocyst trophoblasts. This study was approved by the Medical Ethics Committee of the Hospital (Ethic No.: 2023-23). RESULTS: No abnormality was found on the G-banded karyotyping analysis for both couples. The OGM results revealed that the female partner of couple 1 had a translocation between 4pter-p16.3 (3.99 Mb) and 11pter-p15.4 (2.66 Mb), whilst no abnormality was found in the male partner. Similarly, the male partner of couple 2 had a translocation between 19q13.43-qter (1.90 Mb) and 22q13.31-qter (3.34 Mb). No abnormality was found in the female partner of couple 2. Neither breakpoints nor the adjacent region had involved an OMIM gene, except the formation of a fusion gene ZIM2-AS1-Z82186.1 (Both genes are non-coding, and the fusion gene was deemed as variant of unknown significance). PGT-SR of 11 blastocysts derived from couple 1 revealed that one embryo was suitable for priority transfer, three embryos were suitable for transfer, one embryo was recommended for genetic counselling, and six embryos were unsuitable for the transfer. For couple 2, six blastocysts were tested, of which only one embryo was deemed suitable for transfer. CONCLUSION When genetic testing of offspring indicates copy number variations such as deletions, duplications or mosaicism, the high-resolution OGM technique can be selected to screen parents for submicroscopic chromosomal structural variations. The result can facilitate accurate assessment for the risk of recurrence in offspring, selection of suitable method for reproduction, and identifying targets for PGT.
Humans ; Female ; Pregnancy ; Adult ; Male ; Karyotyping ; Chromosome Aberrations ; Abortion, Habitual/genetics* ; Preimplantation Diagnosis ; Genetic Testing

Objective Observational studies have shown an association between Parkinson disease （PD） and mental illness， but further studies are needed to explore the causal relationship between them. This study aims to investigate such causal relationship using the method of two-sample Mendelian randomization （MR）. Methods Related data were extracted from GWAS， and summary statistics associated with PD， depression， sleep disorders， and anxiety phenotype-variants were obtained. Single nucleotide polymorphisms （SNPs） for PD were selected as instrumental variables， and MR-PRESSO was used to exclude outliers. Inverse variance weighting was used as the main method to assess causal effect estimates， and MR Egger， weighted median， simple mode， and weighted mode were used to verify the robustness of the findings. A sensitivity analysis was used to validate the reliability of the results， including the Cochran Q test， the MR-Egger intercept test， funnel plots， and the leave-one-out method. Results A total of 21 SNPs associated with PD were identified. The MR analysis showed that PD had a causal relationship with depression （OR=0.974，95%CI 0.934‒1.015， P=0.210）， sleep disorders （OR=1.056， 95%CI 0.970-1.149， P=0.211）， and anxiety （OR=0.998， 95%CI 0.996‒1.001， P=0.118）， with no statistical significance. Different MR analyses and sensitivity analyses showed that PD did not directly contribute to the development of mental illness. Conclusion There is no direct causal relationship between PD and depression/sleep disorders/anxiety. In clinical practice， healthcare professionals should pay attention to the mental health of patients with PD. Randomized controlled studies should be conducted in the future to further validate the results of this study.
Depression ; Anxiety

Objective:To compare the efficacy and safety of two induction regimens, homoharringtonine plus venetoclax and azacitidine (VHA) versus venetoclax and azacitidine (VA) , for newly diagnosed acute myeloid leukemia (AML) patients who are elderly or ineligible for intensive chemotherapy.Methods:We retrospectively analyzed the clinical data of 59 newly diagnosed AML patients treated with the VHA or VA regimen at Zhengzhou University Affiliated Cancer Hospital from September 2018 to July 2021. The cohort included 25 males and 34 females, with a median age of 63 years. The overall response rate (ORR) , composite complete remission (CRc) rate [CR+CR with incomplete hematologic recovery (CRi) ], minimal residual disease (MRD) negativity rate, overall survival (OS) , relapse-free survival (RFS) , and adverse events were compared between the two groups. Survival was estimated by the Kaplan-Meier method, and prognostic factors were evaluated using univariable and multivariable Cox regression.Results:At the end of the treatment, the ORR was 88.4% (23/26) in the VHA group [21 CR, 2 partial remissions (PR) ] and 90.9% (30/33) in the VA group (25 CR, 5 PR) , with no significant difference between the groups ( P=0.458) . The MRD negativity rates after one cycle of induction were 73.1% (19/26) in the VHA group and 60.6% (20/33) in the VA group, respectively ( P=0.315) . In the high-risk subgroup, the composite remission rates after one cycle were 78.6% (11/14) with VHA and 50.0% (5/10) with VA ( P=0.143) ; MRD negativity rates were 64.3% (9/14) and 20.0% (2/10) , respectively ( P=0.032) . The main adverse events were myelosuppression, gastrointestinal reactions, and infections during neutropenia. Rates of grade 3-4 neutropenia and decreased hemoglobin were similar between groups, whereas grade 3-4 thrombocytopenia was more frequent with VHA than with VA (76.9% vs 45.5%, P=0.015) . With a median follow-up of 13 months (range, 1-59) , 1 year RFS was 69.9% (95% CI: 53.1%-92.2%) with VHA and 55.6% (95% CI: 40.1%-77.1%) with VA ( P=0.305) . The 1 year OS rates were 91.7% (95% CI: 77.3%-100.0%) and 58.2% (95% CI: 41.7%-81.4%) , respectively ( P=0.024) . Among high risk patients, 1 year RFS and OS were higher with VHA than with VA (RFS: 66.2% vs 37.5%, P=0.046; OS: 85.7% vs 48.0%, P=0.011) . Undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) significantly improved RFS and OS ( P=0.027 and 0.047, respectively) . On multivariable analysis, ELN risk classification and MRD negativity after the first cycle were independent prognostic factors for RFS. Treatment regimen (VHA vs VA) , MRD negativity after the first cycle, and receipt of transplantation were independent prognostic factors for OS. Conclusion:VHA provides clinical benefit in newly diagnosed AML patients who are unfit for intensive chemotherapy and in older adults, with particularly favorable outcomes in high risk patients; sequential allo-HSCT confers additional benefit, and associated adverse events are manageable.

Objective To investigate the association between the TyG index,its modified variants,and the risk of developing colorectal cancer(CRC).Methods This study included a total of 93,177 participants from the 2006 Kailuan Group health examination cohort.Participants were categorized into four quartiles(Q1-Q4)according to their TyG and modified TyG indices.Follow-up began at the baseline examination,with incident CRC as the primary outcome.Participants were censored at the time of CRC diagnosis,death,or the end of the study,whichever occurred first.The dose-response relationship between TyG and its modified indices and the risk of CRC was evalu-ated using restricted cubic splines(RCS)in conjunction with Cox proportional hazards regression models,yielding hazard ratios(HRs)and 95%confidence intervals(CIs).To compare the strength of associations between TyG and its modified versions(TyG-BMI,TyG-WC,TyG-WHR,TyG-WHtR,TyG-WWI)and CRC risk,HRs for CRC per one standard deviation increase in each index were calculated and compared.Results Both the TyG index and its modified variants demonstrated a significant dose-response relationship with the risk of CRC incidence.Specifically,for the TyG index,each 1-standard deviation(SD)increase was associated with a 1.17-fold(95%CI:1.09～1.27)higher risk of CRC.Compared with the first quartile(Q1),the third quartile(Q3)and fourth quartile(Q4)exhibited a 1.25-fold(95%CI:1.01～1.55)and 1.26-fold(95%CI:1.01～1.57)increased risk,respectively.For TyG-BMI,each 1-SD increase was linked to a 1.20-fold(95%CI:1.07～1.35)elevated CRC risk.Compared with Q1,Q3 and Q4 showed a 1.32-fold(95%CI:1.06～1.64)and 1.51-fold(95%CI:1.21～1.88)increase,respectively.Regarding TyG-WC,each 1-SD increment was associated with a 1.22-fold(95%CI:1.13～1.32)higher CRC risk,with Q3 and Q4 showing a 1.35-fold(95%CI:1.08～1.70)and 1.56-fold(95%CI:1.24～1.96)increased risk compared to Q1.For TyG-WHtR,each 1-SD increase was associated with a 1.24-fold(95%CI:1.08-1.42)higher CRC risk.Compared with Q1,Q2,Q3,and Q4 demonstrated a 1.31-fold(95%CI:1.03～1.66),1.55-fold(95%CI:1.23～1.95),and 1.60-fold(95%CI:1.27～2.02)increase,respectively.In the case of TyG-WHR,each 1-SD increase was associated with a 1.19-fold(95%CI:1.10～1.29)higher CRC risk,with Q4 showing a 1.42-fold(95%CI:1.14～1.77)increased risk compared to Q1.Finally,for TyG-WWI,each 1-SD increase was associated with a 1.22-fold(95%CI:1.13～1.32)elevated CRC risk,with both Q3 and Q4 showing a 1.58-fold increase(Q3:95%CI:1.26～1.98;Q4:95%CI:1.25～1.99).Stratified analyses by sex and age consistently revealed significant associations between the TyG index and its modified variants and CRC risk.Furthermore,these indices were independently associated with the incidence of both colon cancer and rectal cancer.Conclusions(1)Elevated levels of the TyG index and its modified variants are independent risk factors for CRC.(2)Both the TyG index and its modified forms demonstrate a significant dose-response association with the incidence of CRC.(3)Among the modified TyG indices,TyG-WWI,TyG-WHtR,TyG-BMI,TyG-WC,and TyG-WHR showed stronger correlations with CRC risk compared to the original TyG index.

Objective To investigate the association between butyrate metabolism-related genes(BMRGs)and the prognosis of lung adenocarcinoma(LUAD),construct a prognostic model,and evaluate its predictive value.Methods Differentially expressed BMRGs(BMR-DEGs)were screened from the TCGA-LUAD dataset.Cox and LASSO regression analyses were employed to establish a risk scoring model,stratifying patients into low-and high-risk groups.The model's performance was assessed using Kaplan-Meier(K-M)and receiver operating characteristic(ROC)curves,with external validation conducted using the GSE68465 dataset.In vitro experiments included RT-PCR and Western blotting to measure insulin-like growth factor binding protein 1(IGFBP1)expression.IGFBP1 was knocked down using siRNA,and its effects on cell proliferation,migration,and invasion were evaluated via CCK-8,colony formation,Transwell,and wound healing assays.Gene Set Enrichment Analysis(GSEA)was performed to explore IGFBP1-related regulatory mechanisms.Results We identified a total of 51 BMR-DEGs,primarily involved in biological processes such as cell proliferation,migration,and invasion,and associated with the PI3K-Akt and MAPK signaling pathways.The constructed 5-gene risk scoring model demonstrated that high-risk patients had significantly worse overall survival(OS)than low-risk patients(P＜0.05).IGFBP1 was highly expressed in LUAD tissues and correlated with poor prognosis.Knockdown of IGFBP1 significantly suppressed cancer cell proliferation,migration,and invasion(P＜0.05).GSEA revealed that IGFBP1 was linked to lipid metabolism-related pathways.Conclusion BMRGs are associated with LUAD prognosis,and the established risk scoring model exhibits strong predictive performance.High IGFBP1 expression correlates with unfavorable outcomes,and its knockdown inhibits cancer cell proliferation,migration,and invasion.

Objective To investigate the role of transcription factor EB(TFEB)in endotoxin-tolerant macrophages.Methods The RAW264.7 cells were divided into blank group(DMEM medium),LPS 5 group(5 ng/mL LPS treatment for 4 h),LPS 100 group(100 ng/mL LPS treatment for 4 h),and tolerance group(5 ng/mL LPS for 12 h followed by 100 ng/mL LPS for 4 h).The releases of inflammatory factors TNF-α and IL-6 were measured using ELISA.Western blotting and immunofluorescence assay were used to evaluate the distribution of autophagy-related proteins LC3 and P62,as well as TFEB in the cytoplasm and nucleus.Lentiviral overexpression of TFEB or siRNA-mediated knockdown of TFEB were performed to observe the changes in autophagy levels and bacterial clearance ability in the tolerant cells.Results The cells in the tolerance group had significantly lower contents of TNF-α and IL-6,as well as reduced bacterial clearance ability(P<0.01),down-regulated LC3 expression while up-regulated P62 level,and decreased expression of TFEB in both the cytoplasm and nucleus(P<0.01)when compared with the cells of the LPS 100 group.Overexpression of TFEB significantly increased LC3 level,reduced P62 level,and enhanced bacterial clearance ability in the endotoxin-tolerant cells(P<0.01).In contrast,siRNA-mediated knockdown of TFEB had no significant impacts on LC3 and P62 expression levels or bacterial clearance ability.Conclusion Overexpression of TFEB can restore the autophagy of endotoxin-tolerant cells and enhance their bacterial clearance capacity,thereby alleviating the immunosuppressive state of sepsis.These findings suggest that TFEB holds promise as a potential therapeutic target for the prevention and treatment of sepsis.

Objective To investigate the role and underlying mechanism of activating transcription factor 3(ATF3)in suppressing lipopolysaccharide(LPS)-induced autophagy and inflammatory responses in macrophages.Methods Firstly,the gene expression omnibus(GEO)database was used to analyze ATF3 expression in peripheral blood mononuclear cells(PBMCs)from sepsis patients,and gene set enrichment analysis(GSEA)was performed to identify enriched signaling pathways.Secondly,RAW264.7 macrophages were divided into a blank control group and an LPS-stimulated group(100 ng/mL LPS).Western blotting and immunofluorescence assay were used to detect ATF3 protein expression and observe its subcellular localization,respectively.Lentiviral transduction was used to generate ATF3 knockdown and overexpression cell lines to evaluate their effects on cytokine release and bacterial clearance.Cleavage Under Targets and Tagmentation(CUT&Tag)sequencing was employed to identify downstream target genes transcriptionally regulated by ATF3.Furthermore,the impact of ATF3 knockdown or overexpression on autophagy-related gene 5(ATG5),autophagy-related gene 16-like 1(ATG16L1),and autophagy levels was evaluated.Results GEO analysis revealed that ATF3 expression was significantly elevated in PBMCs from sepsis patients(P<0.01),and GSEA showed significant enrichment of autophagy-related and inflammation-related pathways(P<0.01).In RAW264.7 cells,100 ng/mL LPS stimulation significantly increased ATF3 expression in the nucleus than the blank control group(P<0.01).ATF3 knockdown led to increased secretions of TNF-α and IL-6 and enhanced bacterial clearance of macrophages(P<0.01),whereas ATF3 overexpression significantly suppressed TNF-α and IL-6 releases,and remained bacterial clearance at a low level when compared with the conditions in the negative control(NC)group(P<0.01).CUT&Tag results demonstrated that ATF3 was enriched at the promoter regions of key autophagy genes Atg5 and Atg16l1.Compared with the NC group,ATF3 knockdown significantly up-regulated the protein levels of LC3-II/I,ATG5,and ATG16L1 while decreased p62 expression(P<0.01).Conversely,ATF3 overexpression inhibited the expression of LC3-II/I,ATG5,and ATG16L1(P<0.01),but had no significant effect on p62 level.Conclusion Sepsis induces elevated ATF3 expression in macrophages,and suppresses autophagic activity and down-regulates pro-inflammatory cytokines TNF-α and IL-6,which probably mediated by ATF3 regulating transcription of ATG5 and ATG16L1,suggesting ATF3 as a potential therapeutic target for autophagy-inflammation imbalance.

Ergonomic Principle for the Prevention of Work-Related Musculoskeletal Disorders Part 1: General Principles (T/WSJD 14.1-2020) is the first guideline standard for the prevention of work-related musculoskeletal disorders provided to employers and occupational health technical service institutions in China, which covers ergonomic risk factors and their hazard definition, ergonomic prevention principles, risk assessment process, risk control process and risk evaluation principles. The standard specifically clarify the specific types of adverse ergonomic risk factors and control strategies and the standard process of systematic ergonomic risk assessment, providing implementation paths and practical guidance for eliminating/reducing adverse ergonomic risks and enhance workplace environments to prevent work-related musculoskeletal disorders. This paper interprets and analyzes the background of standard establishment, formulation process, fundamental basis, and main content, etc., to provide scientific and accurate technical support for enterprise managers, labours and technical personnel of occupational health institutions to optimize the use of this standard.

BACKGROUND:Multiple studies and observations have indicated a close relationship between inflammation,metabolites,and osteoporosis.However,it is still unclear whether there is a genetic causal effect between inflammation-related proteins and osteoporosis and whether metabolites play a mediating role in this process.OBJECTIVE:To investigate the causal relationships between inflammation-related proteins and osteoporosis using Mendelian randomization method as well as the mediating effect of plasma metabolites in this process.METHODS:Summary data from genome-wide association studies(GWAS)were used,with osteoporosis data sourced from the Fengenn database,and GWAS data on inflammation-related proteins and plasma metabolites obtained from published studies.The inverse-variance weighted method was primarily used to assess the exposure-outcome relationships.Bidirectional Mendelian randomization analyses were used to explore the causal relationships between inflammation-related proteins and osteoporosis,and two-step Mendelian randomization was used to discover potential mediating metabolites.Sensitivity analyses were then performed to further validate the robustness of the results.Cochran's Q test was used to assess heterogeneity,and horizontal pleiotropy was evaluated using the MR-Egger intercept and MR-PRESSO methods.RESULTS AND CONCLUSION:The initial bidirectional Mendelian randomization analysis identified five inflammation-related proteins that showed a positive causal relationship with osteoporosis and no reverse causal relationship.Artemin(odds ratio[OR]=0.895,95%confidence interval[CI]:0.819-0.979,P=0.015)was negatively associated with osteoporosis,whereas chemokine(C-X-C Motif)ligand 1(OR=1.100,95%CI:1.002-1.209,P=0.046),chemokine(C-X-C Motif)ligand 11(OR=1.150,95%CI:1.043-1.268,P=0.005),interleukin 17C(OR=1.087,95%CI:1.004-1.176,P=0.040),and tumor necrosis factor-like weak inducer of apoptosis(OR=1.108,95%CI:1.002-1.226,P=0.046)were positively associated with osteoporosis.Sensitivity analyses indicated no heterogeneity or pleiotropy in these causal effects.Subsequently,we conducted a two-step Mendelian randomization to discover potential mediating metabolites.This study showed that 1-palmitoyl-gpc(16:0)increased the negative effect of Artemin on osteoporosis.5α-androstan-3α,17β-diol monosulfate increased the risk of osteoporosis mediated by chemokine(C-X-C Motif)ligand 1 and chemokine(C-X-C Motif)ligand 11.The ratio of α-ketoglutarate to succinate led to an increased risk of osteoporosis mediated by chemokine(C-X-C Motif)ligand 11 and interleukin-17C.Spermidine and the ratio of proline to trans-4-hydroxyproline contributed to an increased risk of osteoporosis mediated by chemokine(C-X-C Motif)ligand 11.12,13-DiHOME contributed to an increased risk of osteoporosis mediated by interleukin-17C.The sulfate level of piperine metabolite C16H19NO3(3)and adenosine 3',5'-cyclic monophosphate contributed to an increased risk of osteoporosis mediated by tumor necrosis factor-like weak inducer of apoptosis.In conclusion,the above data indicate that some inflammation-related proteins can influence the risk of osteoporosis,both positively and negatively,and some of these effects are mediated by plasma metabolites.This provides new insights for future investigations into the occurrence and development mechanisms of osteoporosis.